End-stage renal disease is a catastrophic illness. Recent reports indicate that the incidence of this disorder is increasing at an alarming rate. Treatment of ESRD with hemodialysis is life-saving, however life- expectancy is about 1/4 that of normal individuals after age 40. Furthermore, despite the advent of high-efficiency, biocompatible hemodialyzers, annual mortality rate of patients on chronic dialysis in the U.S. has been increasing and remains much higher than most other industrialized nations. It is not known whether the amount of dialysis, dialyzer biocompatibility or both are in part responsible for this increase in mortality. However, several studies have shown that a low dose of dialysis, estimated by single-pool urea kinetic models using Kt/V, is associated with a higher mortality. Unfortunately, there is considerable uncertainty as to the optimal dose of dialysis. This response to RFA DK- 94-004 describes our competence to serve as a clinical center for the Mortality and Morbidity in Hemodialysis Patients based on our proven ability to recruit and manage patients in multicenter clinical trials. The study will enroll 900 patients who will be randomized to hemodialysis with a 2-pool Kt/V of either 1.3-1.5 or 0.9-1.1 and a dialysis membrane that is either biocompatible or bioincompatible. The dose and delivery of dialysis will be monitored by monthly measurement of Kt/V calculated by a 2-pool model. In addition direct measurement of urea removal will be monitored. The outcome variables will be morbidity and mortality. It is anticipated that this study will: 1) provide information that will improve survival of patients on long-term hemodialysis and 2) improve the ability to estimate the effects of dialysis dose and dialysis membrane on survival.